Clinical trials

A pilot single center randomized trial to test whether a full-scale RCT evaluating the role of post-AHSCT maintenance immunosuppression with MMF in preventing disease relapse is feasible . We are studying whether a brief course of treatment with MMF after AHSCT will serve to prevent disease relapse.

The goal of this randomized clinical trial is to address the uncertainty surrounding blood transfusion strategies in the operating room for adult patients undergoing major surgery. The main question it aims to answer is: Does a higher hemoglobin threshold for blood transfusion during surgery reduce the risk of serious complications or death after surgery compared with a lower hemoglobin threshold? Researchers will compare a liberal and a restrictive transfusion strategy during surgery and the first few hours of recovery. Participants will be randomly assigned to one of two blood transfusion strategies. Blood transfusions will be given to maintain either a higher hemoglobin level (90-100 g/L) or a lower hemoglobin level (70-80 g/L) during surgery and while in the recovery room after surgery. Participants will also complete questionnaires about their quality of life and recovery at 30 and 90 days after surgery.

Cancer-related fatigue (CRF) and cancer-related cognitive impairment (CRCI) are among the most commonly reported disabling symptoms experienced by patients with advanced cancer. However, there are currently limited evidence-based pharmacologic interventions available. The investigators will conduct a Vanguard Randomized Clinical Trial (RCT) to estimate the effect of modafinil in managing CRF and CRCI, and to test the feasibility of carrying out the study.

Patients with acute heart failure (AHF) commonly present to the emergency department (ED) with difficulty breathing and often have poor outcomes or death. Care of AHF is very complex and, unfortunately, there are no specific guidelines for how physicians should manage AHF in the ED. The investigators recently created the Canadian Association of Emergency Physicians (CAEP) AHF Best Practices Checklist, a concise document that provides specific guidance for ED care. Our ultimate goal is to conduct a 12-site cluster study to introduce the CAEP AHF Checklist in multiple EDs. Before the investigators can do so, it is essential to demonstrate feasibility in a smaller-scale study. Our objective for this application is to conduct an internal pilot study to demonstrate feasibility of measuring implementation outcomes and refine the protocol if necessary. The investigators will develop strategies to encourage successful adoption of the Checklist by physicians in the ED and allocate 4 large Ontario EDs to implement the Checklist for 1,700 adult AHF patients. This study will be very important for patients and the healthcare system. If the investigators show that the CAEP AHF Checklist improves patient management and outcomes, this would lead to widespread uptake of the Checklist by all EDs in Canada.

This trial seeks to assess the feasibility of a full-scale, double-blind, placebo-controlled, randomized trial assessing whether low-dose colchicine (0.5 mg daily) reduces the risk of post-thrombotic syndrome (PTS) in patients with proximal lower extremity deep vein thrombosis (DVT).

The investigators are studying whether treatment with a proton pump inhibitor called omeprazole reduces gastrointestinal bleeding in older adults taking blood thinners for a blood clot (venous thromboembolism). The purpose of this study, a pilot study or a feasibility study, is to test the study plan and determine whether enough participants will join a larger study and accept the study procedures.

The REaCT-CHRONO-MetBP Pilot study will compare morning and evening administration of endocrine-based therapy in metastatic breast and prostate cancers. Participants with metastatic breast or prostate cancer will be randomly placed in one of two groups: a morning group and an evening group. The group assignment will determine whether they take their endocrine therapy in the morning or the evening. The primary outcome of this pilot study is to evaluate the feasibility of study procedures in order to conduct a larger definitive trial in the future. The secondary outcomes include comparing quality of life, tolerability, and efficacy outcomes between the morning and evening groups for each of the two cancer cohorts (metastatic breast and prostate cancer).

The body's biological functions follow a circadian rhythm, meaning that individual biological functions in the body change over a 24-hour cycle. There is evidence suggesting that the body and cancer cells may react differently to anti-cancer treatment based on the time of day they are exposed. In fact, researchers have already found that giving anti-cancer treatments at a particular time of the day works better in rectal and ovarian cancer. Temozolomide (TMZ) is a chemotherapy pill/capsule commonly given to patients with newly diagnosed glioblastoma after brain surgery and radiation treatment. However, there is no current standard for what time of day TMZ should be taken for the treatment of glioblastoma. In the current study, participants are randomly placed in one of two groups: a morning group and an evening group. Based on this group placement, participants are instructed to either take their TMZ in the morning or in the evening and record the date and time they take their TMZ in a pill diary. Participants will wear a wrist actigraphy device for the first cycle of TMZ. The primary goal of the study is to understand if taking TMZ at a prescribed time of day (morning/evening) is feasible in adults with glioblastoma. This is a pilot trial, and the investigators hypothesize that it will be feasible for glioblastoma patients to take TMZ at the prescribed time of day. The secondary goals of this study are to evaluate participant recruitment, safety, health-related quality of life, biological timing of TMZ delivery, and changes in condition over time. This pilot study will help investigators plan for a larger, pragmatic randomized clinical trial in the future.

The goal of this clinical trial is to determine whether a renin-guided antihypertensive treatment strategy is feasible to implement in community primary care clinics and to explore whether spironolactone improves blood pressure control in adults with low-renin hypertension. The main questions it aims to answer are: Is it feasible to identify, recruit, randomize, and follow adults with low-renin hypertension in a pragmatic primary care-based clinical trial? Does first-line treatment with spironolactone result in greater reductions in ambulatory blood pressure compared with standard first-line antihypertensive therapy among adults with low-renin hypertension? Researchers will compare spironolactone 25 mg daily with standard first-line antihypertensive therapy (candesartan, hydrochlorothiazide, or amlodipine) to determine whether spironolactone provides better blood pressure control in adults with low-renin hypertension. Participants will: Undergo blood pressure assessments, blood tests, and ambulatory blood pressure monitoring (ABPM) to determine eligibility. Be randomly assigned to receive either spironolactone or a standard first-line antihypertensive medication for 12 weeks. Complete follow-up visits and laboratory testing to monitor blood pressure response, kidney function, electrolyte levels, medication adherence, and side effects. Undergo repeat blood pressure measurements and ABPM at the end of the study.

The goal of this clinical trial is to learn whether bowel preparation powders used before colonoscopy can be taken as capsules instead of being mixed and drunk as a liquid. Bowel preparation is the medicine people take to clean the bowel before a colonoscopy. This study will include adults aged 18 to 75 years who are already scheduled for an outpatient colonoscopy and who have had a colonoscopy before. The main questions this study aims to answer are: 1. Can participants swallow and complete a large number of bowel preparation capsules with the required clear fluids? 2. Can the capsules be prepared accurately and practically by a pharmacy or by participants at home? 3. Is the capsule-based bowel preparation safe and well tolerated? 4. Does the capsule-based bowel preparation clean the bowel well enough for colonoscopy? Participants will take approved bowel preparation products, Pico-Salax or Bi-PegLyte, in vegan hydroxypropyl methylcellulose capsules. They will take the capsules with clear fluids using a split-dose schedule before colonoscopy. The study will happen in three parts. First, researchers will test two capsule sizes using Pico-Salax capsules prepared by a partner pharmacy. Then, researchers will test Bi-PegLyte capsules using the capsule size selected from the first part. Finally, some participants will prepare the capsules themselves at home using study instructions and materials. Researchers will measure how many capsules and how much fluid participants complete, symptoms during preparation, safety blood tests, participant satisfaction, and bowel cleanliness during colonoscopy.

The PRO-Active rehabilitation prior to Kidney Transplantation to ImproVe patient-centered recovery Evaluation trial tests an approach where people are supported to exercise, improve diet, and receive emotional support at home before and after kidney transplant surgery to understand the ideal process and benefits.

Total joint replacement (TJR) has revolutionized care provided for patients suffering from disabling joint pain. Unfortunately, periprosthetic joint infection (PJI) remains a devastating complication and the leading cause of failure after TJR. Current standard treatment for PJI requires multiple surgical revisions of the infected prosthesis in combination with a prolonged course of systemic antibiotic therapy. Debridement Antibiotic and Implant Retention (DAIR) procedure is one of the surgical options that is routinely used to manage PJI, due to its lower risk of morbidity and surgical cost. DAIR is often used for patients who present with an acute PJI or who cannot tolerate a complex implant revision. However, the overall success rate for DAIR is ranging between 60-70%. DAIR failures are often attributed to the residual infection and biofilm burden left behind on the retained implant surface, which cannot be targeted effectively with post-operative systemic antibiotics. Therefore, research has been ongoing to identify non-surgical multidrug resistance (MDR) treatment adjuncts that can synergize the therapeutic effects of antibiotics in PJI care. Numerous preclinical bone and joint infection models have clearly demonstrated such therapeutic benefits using bacteriophages (phages). Phages target bacterial cells and breakdown biofilm that it forms on the implant surface. Each bacterial strain tends to have a particular phage that is susceptible to that bacterial strain. Due to this phage specificity and the fact that bacteria can still develop resistance against a single phage, the concept of using a phage cocktail (mixture of 2 or more phage candidates) has been the preferred treatment approach for applying phage therapy. Using a phage cocktail provides a broader spectrum of bacterial strain coverage and makes it harder for the bacteria to develop resistance. Published literature has considered phage therapy to be safe for direct administration at the infection site with minimal adverse events provided that the phage preparation administered meets Good Manufacturing Practice (GMP). The DePHEAT PJI trail, is a prospective, single center, 1:1 non-blinded feasibility randomized controlled trial (RCT) that aims to assess the safety and the effectiveness of the experimental phage therapy cocktails for patients with hip or knee PJI caused by either Staphylococcus (S.) aureus or Pseudomonas (P.) aeruginosa and comparing it to standardized therapy. The investigator hypothesizes that this pilot RCT will help evaluate the practicality and potential risks associated with adding phage therapy to the conventional standard of care treatment plan. This will initiate the development of a necessary infrastructure for future phage trials and programs that expand our understanding on the benefits of using phage therapy for acute PJI.

The Advancing Cognition and Cognitive reserve before ELective surgery to Enhance cognitive Recovery And TrajEctories (ACCELERATE) Pilot Trial estimates whether our novel, coach-supported cognitive prehabilitation strategy will achieve adequate intervention adherence in the context of a feasible multicenter trial protocol.

The goal of this randomized, pragmatic clinical trial is to evaluate the omission of granulocyte colony-stimulating factors (G-CSF) in breast cancer patients receiving paclitaxel portion of dose-dense adriamycin-cyclophosphamide and paclitaxel (DD-AC/T) chemotherapy. Participants will be randomized to either take G-CSF while on the paclitaxel portion of DD-AC/T chemotherapy or to omit G-CSF while on the paclitaxel portion of DD-AC/T chemotherapy.

Cellulitis is a painful bacterial skin infection commonly seen in Canadian emergency departments. Cellulitis has a negative impact on patients' quality of life and productivity. While this is a bacterial infection, there is evidence inflammation also contributes to the disabling symptoms of pain, redness and swelling. Some studies have suggested that a nonsteroidal anti-inflammatory drug (NSAID) such as naproxen in addition to antibiotics may control inflammation and speed recovery. However, these studies have had too few patients to tell if there is a true benefit. The investigators are proposing a randomized controlled trial of patients with cellulitis to compare oral naproxen (500 mg twice daily) plus oral antibiotics versus placebo plus oral antibiotics. The investigators will compare the proportion of patients who have an early clinical response (reduction in area of redness ≥20% at 72 hours), cure, treatment failure, adverse events, and hospital admission. If naproxen proves to be superior to placebo, this simple, low-cost intervention will speed time to recovery with less pain for patients, and may potentially reduce treatment failure and time missed from activities. The results of this trial will help inform future cellulitis treatment guidelines.

This is a single-site, open-label, randomized pilot feasibility study conducted at The Ottawa Hospital Cancer Centre. A total of 10 participants will be randomized 1:1 to either the experimental or control arm. The purpose of this study is to evaluate recruitment capability, intervention adherence, data completeness, and safety prior to consideration of a potential future multi-centre randomized trial.

This is a single patient study (SPS) that aims to test the bacteriophage treatment as an experimental treatment on a patient suffering from chronic periprosthetic joint infection (PJI) of the right hip. This patients has been suffering from an infection in the right sided hip arthroplasty with a multidrug resistant (MDR) strain of Pseudomonas aeruginosa bacteria. All treatment options for this type of infection have been exhausted. If this patient remains without treatment then there is a high risk of mortality secondary to sepsis and the only remaining surgical option for this patient is a hind quarter amputation which will be a devastating surgery that will largely affect this patients quality of life. However, a large number of published case series have shown the positive impact of combining bacteriophage therapy with antibiotics to achieve a synergistic antibacterial effect and overcome possible resistance development to clear the infection. Therefore the investigators intend to try the bacteriophage therapy on this patients infected hip in the aim to control the infection and improve the patients quality of life.

A prospective, multi-center, double-arm, parallel, interventional, randomized, controlled clinical trial to assess the rate of periprosthetic joint infection (PJI) in patients undergoing primary total knee arthroplasty (TKA), total hip arthroplasty (THA) or hip resurfacing (HR) with XPERIENCE™ (XP) Advanced Surgical Irrigation versus dilute Betadine (DB).

The current standard of care for stage 1 hormone receptor-positive (HR+) breast cancer consists of breast-conserving surgery followed by adjuvant radiotherapy (RT) and endocrine therapy (ET) for at least 5 years. The benefit of adjuvant ET for older patients is mitigated because of their increase risk of death from other causes and shorter time horizon to live. Clinical and pathological factors such as low-intermediate grade, tumor size ≤2 cm, and older age have been used in a few studies to identify patients with a lower risk of recurrence that might benefit from adjuvant therapy de-escalation, i.e. omission of RT or ET. Since there is no dedicated randomized clinical trial (RCT) conducted to evaluate the omission of ET, there is clinical equipoise as to whether we can omit adjuvant ET in older patients with lower-risk early-stage breast cancer. Therefore, we propose a randomised, multicentre trial evaluating harms and benefits of endocrine therapy in patients ≥70 years of age with lower risk breast cancer.

The standard treatment for Type 2 diabetes involves management of the disease based on average of blood glucose control over the past few months. In this study, the investigators test for the participants' ability to produce insulin, which is the hormone that the body makes to control blood sugar levels. The body produces insulin in response to eating. The participants will drink a meal replacement shake, and then test the blood for levels of insulin produced over 2 hours. With blood tests taken five times over two hours, the investigators will measure the blood glucose (sugar), and insulin levels. This study will assess the differences in insulin produced in the participants and try to understand the reasons for these differences.

Major thoracic surgery is high risk as it carries a significant risk of postoperative Adverse Events (AEs), where patients experience complications and do not recover as expected. These AEs can increase the risk of mortality, hospital length of stay, as well as healthcare costs. The investigators' aim is to improve surgical safety by pioneering a marked advance in preoperative prediction of postoperative AEs that will enable individualized targeted perioperative pathways to prevent postoperative AEs. Given that illness and stress are associated with a loss in physiologic variability (e.g. heart and respiration rate), the investigators will use heart and lung variability assessments to improve prediction of postoperative AEs. Therefore, this study aims to assess the feasibility of implementing a preoperative CardioPulmonary variability assessment; determine if preoperative CardioPulmonary variability is associated with postoperative AEs; and determine if this variability assessment is superior and complementary to existing measures of risk and frailty.

The STRIVE Before Surgery Trial evaluates patient-reported disability at 90 days after surgery following participating in a home-based multimodal prehabilitation program supported through an online platform. Half of the participants will be randomized into the prehabilitation group, while the other half will be randomized into the control group.

Timely and safe extubation in critically ill patients is vitally important as prolonged mechanical ventilation and failed attempts at extubation are associated with increased morbidity, mortality, costs, intensive care unit (ICU) stays, and a risk for aerosolization of COVID-19 to health care providers. A Spontaneous Breathing Trial (SBT) is the current standard of care to assess a patient's readiness for extubation. However, SBTs are performed in various ways and have poor ability to predict successful extubation on their own. There is an urgent need to improve and standardize extubation decision-making. In a prior multicenter study, the investigators showed that decreased respiratory rate variability during SBTs predicted extubation failure better than other predictive indices. The Extubation Advisor (EA) tool combines clinician's assessments of extubation readiness with predictive analytics and risk mitigation strategies for individual patients. In a single centre observational study, the investigators demonstrated the ability to deliver EA reports to the bedside and acceptability of this decision-support tool to respiratory therapists (RTs) and physicians (MDs). The investigators will conduct the Liberation from mechanical ventilation using EA Decision Support (LEADS) Pilot Trial to assess feasibility outcomes. They will include critically ill adults who are invasively ventilated for \>48 hours and are ready to undergo an SBT. Patients in the intervention arm undergo an EA assessment and treating clinicians (RTs, MDs) will receive an EA report for each SBT conducted. The EA report will help to guide extubation decision-making. Patients in the control arm receive standard care. SBTs will be directed by clinicians. The primary feasibility outcome will reflect the ability to recruit the desired population. The investigators will also assess the usefulness of the tool to MDs and complete an analysis of resource utilization to inform future economic analyses of cost-effectiveness. The investigators aim to recruit 1 to 2 patients/month/center. The LEADS trial is novel and low-risk. It is the first trial to evaluate use of a bedside decision support tool to assist ICU clinicians with extubation decision-making. The LEADS pilot trial will inform the design of a future, large-scale randomized controlled trial that is expected to enhance the care delivered to critically ill patients, improve extubation outcomes, and inform extubation practice in ICUs.

Atrial Fibrillation (AF) affects 200,000 Canadians and increases risk of stroke, morbidity and mortality. Having a stroke can affect a patient's ability to speak, eat, walk, work, care for themselves, and interact with others. Not only can it ruin one's life, but it can also be fatal. A stroke occurs when blood flow to the brain is blocked by a clot, depriving brain cells of oxygen. In people with atrial fibrillation, blood flow is sluggish in the top chambers of the heart, and blood clots can form there. When a piece of a clot breaks off, it can travel to the brain and cause a stroke. That's where blood thinners come in. Blood thinners, or anticoagulants, decrease the chances of blood clots forming in the heart, reducing the risk of stroke. Studies show that blood thinners are highly effective at reducing the risk of stroke by up to 95%. The conventional blood thinner is warfarin, taken by mouth. Warfarin requires regular blood tests to make sure a patient getting the correct dose. The patient also may have to avoid certain foods since the medication can interact with them. Newer blood thinners, known as direct-oral anticoagulants (DOACs) are available, which do not require regular blood tests and do not interact with foods. Two of the new blood thinners are called rivaroxaban and apixaban. Like warfarin, they can be taken by mouth, and studies have shown them to be as effective as warfarin. Both rivaroxaban and apixaban have been approved for stroke prevention in AF by Health Canada. However, there have been no direct head-to-head comparisons of these two anticoagulants, meaning comparative safety data is not available. Increasing use of DOACs for stroke prevention in AF and patient values around bleeding highlight the need for a comparison trial to ensure patients receive the anticoagulant with the greatest balance of benefit to potential harm. The trial is to assess bleeding rates and superiority of using apixaban versus rivaroxaban in patients with non-valvular atrial fibrillation.

Knee replacement surgery is a common and effective treatment for pain and mobility loss, yet up to 1 in 5 patients remain dissatisfied after surgery due to ongoing pain or difficulty with daily activities. Currently, clinicians cannot reliably predict which patients will experience these challenges. This study uses MRI scan of the brain to investigate whether specific patterns of brain activity can predict patient satisfaction after total knee arthroplasty (TKA). By comparing brain networks before surgery and afterward, and linking these changes to patient-reported pain and function, we aim to identify brain-based markers that can help predict outcomes, to improve satisfaction after knee replacement surgery.